2024
Nuclear PKM2 binds pre-mRNA at folded G-quadruplexes and reveals their gene regulatory role
Anastasakis D, Apostolidi M, Garman K, Polash A, Umar M, Meng Q, Scutenaire J, Jarvis J, Wang X, Haase A, Brownell I, Rinehart J, Hafner M. Nuclear PKM2 binds pre-mRNA at folded G-quadruplexes and reveals their gene regulatory role. Molecular Cell 2024, 84: 3775-3789.e6. PMID: 39153475, PMCID: PMC11455610, DOI: 10.1016/j.molcel.2024.07.025.Peer-Reviewed Original ResearchRNA-binding proteinsPre-mRNANon-canonical RNA-binding proteinsGene regulatory roleCancer cellsRNA G-quadruplexesG-quadruplexInvasion of cancer cellsTriple-negative breast cancer cellsBreast cancer cellsEpithelial-to-mesenchymal transitionCancer typesNuclear localizationPrecursor mRNANuclear accumulationGene expressionXenograft mouse modelNuclear PKM2Regulatory roleRG4sPKM2Reduced migrationMouse modelTumor progressionPatient survival
2021
Substance P Antagonism as a Novel Therapeutic Option to Enhance Efficacy of Cisplatin in Triple Negative Breast Cancer and Protect PC12 Cells against Cisplatin-Induced Oxidative Stress and Apoptosis
Rodriguez E, Pei G, Zhao Z, Kim S, German A, Robinson P. Substance P Antagonism as a Novel Therapeutic Option to Enhance Efficacy of Cisplatin in Triple Negative Breast Cancer and Protect PC12 Cells against Cisplatin-Induced Oxidative Stress and Apoptosis. Cancers 2021, 13: 3871. PMID: 34359773, PMCID: PMC8345440, DOI: 10.3390/cancers13153871.Peer-Reviewed Original ResearchTriple-negative breast cancerSP-receptor antagonismTriple-negative breast cancer cell linesTherapeutic optionsBreast cancerSP receptorsCell linesFlow cytometryTriple negative breast cancerCisplatin-induced oxidative stressTriple-negative breast cancer cellsSubstance P antagonismEfficacy of cisplatinGenes associated with metastasisNegative breast cancerHigh-affinity SP receptorResponse to cisplatinCisplatin-inducedNeuronal cell lineTreatment strategiesProduction of reactive oxygen speciesCisplatinPC12 cellsCell cycle progressionReactive oxygen species
2020
Multi-Omics Investigation of Innate Navitoclax Resistance in Triple-Negative Breast Cancer Cells
Marczyk M, Patwardhan GA, Zhao J, Qu R, Li X, Wali VB, Gupta AK, Pillai MM, Kluger Y, Yan Q, Hatzis C, Pusztai L, Gunasekharan V. Multi-Omics Investigation of Innate Navitoclax Resistance in Triple-Negative Breast Cancer Cells. Cancers 2020, 12: 2551. PMID: 32911681, PMCID: PMC7563413, DOI: 10.3390/cancers12092551.Peer-Reviewed Original ResearchTriple-negative breast cancer cellsCancer cellsBreast cancer cellsStress response genesMulti-omics landscapeCell population compositionDrug-induced cell deathMulti-omics investigationsCell linesBCL2 family inhibitorsSingle-cell analysisChromatin accessibilityGenome structureMDA-MB-231 triple-negative breast cancer cellsChromatin structureMethylation stateResponse genesFamily inhibitorsCell deathTNBC cell linesNumber variationsDefense mechanismsResistance mechanismsNew therapeutic strategiesGenes
2019
KPT-9274, an Inhibitor of PAK4 and NAMPT, Leads to Downregulation of mTORC2 in Triple Negative Breast Cancer Cells
Cordover E, Wei J, Patel C, Shan N, Gionco J, Sargsyan D, Wu R, Cai L, Kong A, Jacinto E, Minden A. KPT-9274, an Inhibitor of PAK4 and NAMPT, Leads to Downregulation of mTORC2 in Triple Negative Breast Cancer Cells. Chemical Research In Toxicology 2019, 33: 482-491. PMID: 31876149, PMCID: PMC9316853, DOI: 10.1021/acs.chemrestox.9b00376.Peer-Reviewed Original ResearchConceptsCell growthSerine/threonine kinase mTORNicotinamide phosphoribosyltransferaseBreast cancer cellsTNBC cellsRegulation of RictorPak4 protein kinaseCancer cellsInhibition of PAK4Triple-negative breast cancerTriple-negative breast cancer cellsMTORC2 signalingKinase mTORProtein kinaseRNA sequencingTNBC cell growthNegative breast cancer cellsCell metabolismRictorPAK4Overexpressing cellsSpecific inhibitorDruggable targetsMTOR pathwayInhibits growth
2014
A gemcitabine sensitivity screen identifies a role for NEK9 in the replication stress response
Smith S, Petrova A, Madden M, Wang H, Pan Y, Warren M, Hardy C, Liang D, Liu E, Robinson M, Rudra S, Wang J, Ehdaivand S, Torres M, Wang Y, Yu D. A gemcitabine sensitivity screen identifies a role for NEK9 in the replication stress response. Nucleic Acids Research 2014, 42: 11517-11527. PMID: 25217585, PMCID: PMC4191414, DOI: 10.1093/nar/gku840.Peer-Reviewed Original ResearchConceptsReplication stress responseReplication stressDNA replicationStress responseCell cycle checkpoint pathwaysDNA replication blocksSynthetic lethal screenHuman triple-negative breast cancer cellsGenome integrityReplication arrestTriple-negative breast cancer cellsMitosis geneReplication blocksDNA repairChk1 activityKinase 9Checkpoint pathwayKinase activityNuclear enzymeBreast cancer cellsDNA damageGemcitabine sensitizationCHK1 autophosphorylationNek9Protein levels
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